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The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT an...

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Detalles Bibliográficos
Autores principales: Boubred, Farid, Daniel, Laurent, Buffat, Christophe, Tsimaratos, Michel, Oliver, Charles, Lelièvre-Pégorier, Martine, Simeoni, Umberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129242/
https://www.ncbi.nlm.nih.gov/pubmed/27899104
http://dx.doi.org/10.1186/s12967-016-1086-3
Descripción
Sumario:BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause. METHODS: Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring). RESULTS: Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (−50% in males and −40% in females, p < 0.01), an impaired GFR (−33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (−28% vs. NBW offspring, p < 0.05). CONCLUSION: In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required.